| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GNE-049 primarily targets the bromodomain of CREB-binding protein (CBP), a histone acetyltransferase that plays a critical role in transcriptional co-activation. CBP and its closely related homolog p300 are epigenetic readers that recognize acetylated lysine residues on histone tails and facilitate the assembly of transcriptional complexes. GNE-049 also inhibits BRET (BRD4-associated) with an IC50 of 12 nM and shows weaker activity against BRD4 with an IC50 of 4200 nM, indicating significant selectivity for CBP over BRD4. The compound's high potency and selectivity make it a valuable tool for dissecting the specific functions of CBP/p300 in cellular processes such as proliferation, differentiation, and oncogenesis.
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| ln Vitro |
GNE-049 was chosen for additional examination due to its ideal combination of cellular potency, selectivity, and liver microsomal (LM) stability. GNE-049 performs well in orthogonal assessments of target engagement and demonstrates great potency in BRET cell tests. Among them, GNE-049 has an EC50 of 14 nM and can suppress MYC (MV4-11 cell line) expression[1].
GNE-049 demonstrates potent in vitro activity against CBP with an IC50 of 1.1 nM in TR-FRET biochemical assays. The compound also inhibits BRET with an IC50 of 12 nM. In cellular models, GNE-049 effectively inhibits prostate cancer cell proliferation. The compound's high selectivity for CBP over BRD4 (approximately 3800-fold) minimizes off-target effects and allows for the specific interrogation of CBP/p300-dependent transcriptional programs. GNE-049 has been shown to modulate gene expression patterns associated with CBP/p300 activity, making it a valuable tool for studying the role of these epigenetic regulators in cancer and other diseases. |
| ln Vivo |
GNE-049 has PK that is acceptable in dogs, monkeys, rats, and mice. Potency experiments with respect to specific bromodomains show that GNE-049 exhibits a strong degree of selectivity for CBP/P300 and, crucially, a 3820-fold increase in selectivity over BRD4 (1). In a single-dose (30–250 mg/kg QD) toxicokinetic study conducted on rats, GNE-049 was further assessed. Rats given a dosage of 250 mg/kg showed adverse effects on the central nervous system (CNS), such as vocalization and noticeable hyperactivity. Moreover, the ratio of the unbound drug concentration in the brain to the unbound drug concentration in plasma (Kp,uu) three hours after the injection was found to be 0.43 at the 250 mg/kg dose level, suggesting that GNE-049 is entering the brain. central nervous system and could be a factor in the toxicity that has been reported [1].
GNE-049 has demonstrated in vivo efficacy in prostate cancer models. The compound effectively inhibits tumor growth in preclinical models, confirming the therapeutic potential of CBP/p300 inhibition in cancer. In vivo studies have shown that GNE-049 can suppress tumor progression and modulate biomarkers of CBP/p300 activity. The compound is suitable for oral administration and has been formulated for in vivo use. Detailed in vivo efficacy data, including specific tumor growth inhibition rates and dosing regimens, are available in the primary literature. The compound's ability to inhibit CBP/p300 in vivo makes it a valuable tool for validating the role of these epigenetic regulators in disease pathogenesis. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for GNE-049 is a TR-FRET (time-resolved fluorescence resonance energy transfer) assay that measures the binding affinity of the compound to the bromodomain of CBP. In this assay, a fluorescently labeled acetylated histone peptide is used as the substrate, and the CBP bromodomain is labeled with a terbium chelate. Binding of the peptide to the bromodomain brings the fluorophore and terbium donor into close proximity, resulting in energy transfer and a TR-FRET signal. GNE-049 competes with the peptide for binding to the bromodomain, leading to a decrease in the TR-FRET signal. The IC50 value of 1.1 nM is determined by incubating varying concentrations of GNE-049 with the assay components and measuring the fluorescence signal. The compound is dissolved in DMSO and diluted in assay buffer for testing.
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| Cell Assay |
The in vitro cellular assay for GNE-049 is typically performed using cancer cell lines that are dependent on CBP/p300 activity for proliferation, such as prostate cancer cell lines. Cells are cultured in appropriate medium and treated with varying concentrations of GNE-049 (typically ranging from nanomolar to micromolar) or vehicle control (DMSO) for specified time points (e.g., 72 hours). Cell viability is assessed using assays such as MTT, CellTiter-Glo, or by direct cell counting. Proliferation inhibition is quantified and dose-response curves are generated to determine the EC50. Additionally, the effects of GNE-049 on CBP/p300-dependent gene expression can be assessed by qRT-PCR or RNA sequencing to confirm target engagement and pathway modulation. The compound's effects on cell cycle progression and apoptosis can also be evaluated by flow cytometry.
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| Animal Protocol |
In vivo animal experiments with GNE-049 are typically conducted using immunocompromised mice bearing human cancer xenografts, particularly prostate cancer models. Cancer cells are implanted subcutaneously into the flank of nude or SCID mice. When tumors reach a predetermined size (e.g., 100-200 mm³), animals are randomized into treatment groups receiving GNE-049 or vehicle control. GNE-049 is administered orally (PO) at various doses (e.g., 10-100 mg/kg) on a daily or scheduled basis. Tumor volume is measured twice weekly using calipers, and body weight is monitored to assess tolerability. At the end of the study, tumors are harvested for analysis of CBP/p300 target engagement, histone acetylation status, and downstream gene expression. Pharmacodynamic biomarkers are assessed to confirm target modulation.
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| ADME/Pharmacokinetics |
GNE-049 is soluble in DMSO at 100 mg/mL (195.85 mM) and in ethanol at 3 mg/mL, but is insoluble in water. For in vivo oral administration, GNE-049 can be formulated as a homogeneous suspension in CMC-Na at ≥5 mg/mL. For injection, formulations using 5% DMSO, 40% PEG300, 5% Tween 80, and 50% ddH2O have been validated, yielding a clear solution at 5 mg/mL. Alternatively, a formulation of 5% DMSO in 95% corn oil can be used. The compound should be stored at -20°C under dry, dark conditions. Detailed PK parameters such as half-life, clearance, bioavailability, and maximum concentration are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for GNE-049 are not extensively documented in publicly available sources. As a research-grade compound, GNE-049 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. In animal studies, GNE-049 has been reported to be tolerated at the doses tested, but comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets. The compound should be handled with care and in accordance with institutional safety guidelines.
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| References | |
| Additional Infomation |
GNE-049 is a highly potent and selective CBP/p300 bromodomain inhibitor developed for studying epigenetic regulation in cancer and other diseases. The compound's exceptional potency (IC50 = 1.1 nM) and selectivity for CBP over BRD4 (approximately 3800-fold) make it a valuable tool for dissecting the specific functions of CBP/p300 in transcriptional regulation. GNE-049 has demonstrated efficacy in prostate cancer models, validating CBP/p300 as a therapeutic target. The compound is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical epigenetic research. GNE-049 is available from various chemical suppliers for research purposes. Its high potency and selectivity profile make it a preferred tool for studying CBP/p300-dependent biology.
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| Molecular Formula |
C27H32F2N6O2
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|---|---|
| Molecular Weight |
510.5788
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| Exact Mass |
510.255
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| CAS # |
1936421-41-8
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| PubChem CID |
121373418
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
37
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| Complexity |
816
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC([H])(C1=C(C2C([H])=NN(C([H])([H])[H])C=2[H])C([H])=C2C([H])([H])C([H])([H])C([H])([H])N(C2=C1[H])C1C2C([H])([H])N(C(C([H])([H])[H])=O)C([H])([H])C([H])([H])C=2N(C2([H])C([H])([H])C([H])([H])OC([H])([H])C2([H])[H])N=1)F
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| InChi Key |
FLTYKXCCCAPRLV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H30F2N6O2/c1-16(35)32-8-5-23-22(14-32)26(30-34(23)19-6-9-36-15-19)33-7-3-4-17-10-20(18-12-29-31(2)13-18)21(25(27)28)11-24(17)33/h10-13,19,25H,3-9,14-15H2,1-2H3
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| Chemical Name |
1-[3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-tetrahydrofuran-3-yl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]ethanone
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| Synonyms |
GNE-049; GNE 049; GNE049.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~195.86 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9586 mL | 9.7928 mL | 19.5856 mL | |
| 5 mM | 0.3917 mL | 1.9586 mL | 3.9171 mL | |
| 10 mM | 0.1959 mL | 0.9793 mL | 1.9586 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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